Biologic Therapies in Spondyloarthritides—The Current State
Barend J. van Royen, Ben A. C. Dijkmans in Ankylosing Spondylitis Diagnosis and Management, 2006
In another recent study, sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and during therapy (72). Initially, 32 of 62 RA patients (51.6%) and six of 35 SpA (17.1%) patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 82.3% and 88.6%, respectively. At baseline, none of the RA or SpA patients had anti-dsDNA antibodies. After infliximab treatment, seven RA and six SpA patients became positive for anti-dsDNA antibodies. All seven antidsDNA-positive RA patients had IgM and IgA anti-dsDNA antibodies. During the observation period, no IgG anti-dsDNA antibodies or lupus-like symptoms were observed. The development of anti-nucleosome, anti-histone, or anti extractable nuclear antigen (ENA) antibodies following infliximab treatment was observed in some patients, but the numbers were not statistically significant. Taken together, development of ANA is a rather frequent event in patients on infliximab therapy, while anti-DNA antibodies occur infrequently and is only rarely associated with lupus-related symptoms. In the one year follow-up study of AS patients treated with infliximab we also observed an increase in the percentage of patients becoming ANA-positive while there was no increase in our one year follow-up study in AS patients treated with etanercept (29,48,73).
Anti-L3T4 Antibody Therapy in Systemic Lupus Erythematosus
Thomas F. Kresina in Monoclonal Antibodies, Cytokines, and Arthritis, 2020
Despite the delay in target cell clearance, treatment with anti-L3T4 had an immediate effect on autoimmunity. Before starting therapy, the concentration of anti-dsDNA antibodies had been increasing in both experimental groups (Fig. 6). During the treatment course, the mean titer continued to rise in the saline control group, but in the group that received anti-L3T4, the concentration of anti-dsDNA antibodies immediately plateaued and then dramatically fell. After 2 months of therapy, the mean anti-dsDNA titer in the control group was 1:1300, compared to 1:250 in the anti-L3T4-treated group (p < 0.02).
Rheumatic Disease
John S. Axford, Chris A. O'Callaghan in Medicine for Finals and Beyond, 2023
Autoantibodies: Autoantibodies to nuclear and cytoplasmic antigens may be present (see Table 4.1). The antinuclear antibody (ANA) test is the best screening test for lupus as it is usually positive. Anti-dsDNA antibodies are specific for lupus and may reflect disease activity, while RF is found in 30–50% of patients. Anti-Smith RNA antibodies are also virtually confined to individuals with lupus but are present in less than 20% of such patients.
Emerging targets for the treatment of lupus erythematosus: There is no royal road to treating lupus
Published in Modern Rheumatology, 2019
ETI-104 is a heteropolymer comprising anti-complement receptor 1 antibody and dsDNA, and it is designed to link antoantibodies to complement receptor on red blood cells. Theoretically, anti-dsDNA antibodies are captured and clarified by the reticuloendothelial system. FTI-104 was administered to six patients with SLE, resulting in transient reduction of anti-dsDNA antibodies in three and sustained reduction in three [37]. However, a follow-up clinical trial has not been reported. Abetimus is a tetramer comprising identical dsDNA strands. In a phase-III trial of patients with lupus nephritis, treatment with weekly administration of abetimus significantly reduced anti-dsDNA antibody levels but did not significantly prolong the time to renal flare when compared with placebo [38]. Based on this and other studies, development of abetimus was discontinued as a drug for SLE.
Mitochondria as a key player in systemic lupus erythematosus
Published in Autoimmunity, 2022
Diana C. Quintero-González, Marcela Muñoz-Urbano, G. Vásquez
Since the last decade, NETosis has been recognized as a pathway involved in multiple autoimmune diseases, including SLE. Neutrophile extracellular traps (NET) from patients with SLE are produced faster and at higher magnitudes than those from healthy controls. The lower degradation of NET due to less effective nuclease function also allows persistent exposure of modified autoantigens, which perpetuates the autoimmune response [82,83]. As previously mentioned, ox-mDNA is highly immunogenic and is associated with NETosis [84]. In a study on neutrophils from patients with lupus, exposure to RNP immunocomplexes induced ox-mDNA, drove NETosis in low-density granulocytes, and released IFN I through the STING pathway [60]. Likewise, enhanced expression of the mtDNA immunocomplex is more potent in stimulating pDCs than the dsDNA immunocomplex by binding to Fcvia toll like receptor 9. A better correlation was observed between anti‐mtDNA antibodies and the severity of lupus nephritis compared to that with anti-dsDNA antibodies. Recently, a SNP in the NCF1 gene (NCF-339) was reported to decrease nicotinamide adenine dinucleotide phosphate oxidase (NADPH) isoform 2 and reduce the quantity of NET, confirming the significant dependence of mROS on this immune mechanism in patients with lupus [85].
IgA autoantibodies directed against self DNA are elevated in cystic fibrosis and associated with more severe lung dysfunction
Published in Autoimmunity, 2020
Ruchi Yadav, Rachel W. Linnemann, Joanne Michelle Kahlenberg, S. Louis Bridges, Arlene A. Stecenko, Balázs Rada
Our report detects elevated levels of autoantibodies targeting human host dsDNA in CF. While the presence of these antibodies in CF is novel, SLE, a systemic and poly-etiological autoimmune disease, is characterized by high titres of autoantibodies directed against nuclear components including DNA [13]. Antibodies targeting host dsDNA are prognostic markers in SLE [13]. Generation of anti-dsDNA antibodies requires first that dsDNA normally found inside of cells hidden from the immune system is released into the extracellular environment. Different routes of cell death have been proposed as the main mechanism of dsDNA release in SLE. Although impaired clearance of apoptotic cells has been proposed originally as its main mechanism in SLE [30], recently neutrophils and formation of NETs have gained most of the attention. Rather than being a protective mechanism, a long line of evidence suggests the relevance of neutrophils and NETs in SLE pathogenesis [31].
Related Knowledge Centers
- Antinuclear Antibody
- DNA
- Elisa
- Lupus Nephritis
- Phagocyte
- Apoptosis
- Antigen
- Lupus
- Le Cell
- Immune Response